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Chloramphenicol metabolism in children with protein-calorie malnutrition
Insights
Malnourished children exhibit significantly higher plasma chloramphenicol levels and prolonged drug clearance due to slower liver biotransformation. This impacts drug metabolism and excretion in pediatric populations.
Area of Science:
- Pharmacokinetics
- Pediatric Medicine
- Drug Metabolism
Background:
- Chloramphenicol is an antibiotic requiring careful dosage, especially in vulnerable populations.
- Malnutrition can alter drug pharmacokinetics, affecting efficacy and safety.
- Understanding chloramphenicol metabolism in malnourished children is crucial for optimizing treatment.
Purpose of the Study:
- To investigate the plasma levels and urinary excretion of chloramphenicol in malnourished versus normal children.
- To elucidate the impact of malnutrition on chloramphenicol biotransformation and clearance rates.
Main Methods:
- Oral administration of a single 25 mg/kg dose of chloramphenicol to ten malnourished and four normal children.
- Monitoring of plasma drug concentrations over time.
- Analysis of urinary excretion patterns, including conjugated and unconjugated metabolites.
- Assay of liver bilirubin-UDP transferase activity in a subset of participants.
Main Results:
- Malnourished children showed 1.5-2 times higher peak plasma chloramphenicol levels compared to normal children.
- Drug elimination was significantly prolonged in malnourished children (≥30 hours) versus normal children (12 hours).
- Urinary excretion revealed a lower percentage of conjugated chloramphenicol in malnourished children (35-55%) compared to normal children (75-85%).
- Reduced bilirubin-UDP transferase activity was detected in liver biopsies from two malnourished children.
Conclusions:
- Malnutrition significantly impairs chloramphenicol biotransformation and clearance in children, likely due to reduced liver enzyme activity.
- Altered drug metabolism in malnourished children necessitates careful consideration of dosing regimens to prevent toxicity.
- Findings highlight the importance of assessing nutritional status when prescribing chloramphenicol to pediatric patients.
Abstract:
The plasma levels and urinary excretion of chloramphenicol was studied in ten malnourished children and four normal children after oral administration of a single dose of 25 mg/kg body weight. Plasma peak levels were achieved 2-4 hours later and were 1.5 or 2 times higher in malnourished children compared to the normal. They also took much longer to clear the drug from the plasma, 30 hours or more in malnourished children compared with 12 hours in the normal. These observations point to a slower rate of biotransformation in the liver. The excretion pattern of the drug and its metabolite lends support to this hypothesis. 75-85% of the drug excreted was in the form of conjugated fraction in the normal while only 35-55% was conjugated in malnourished children. In two children the liver biopsy tissue was subjected to assay of bilirubin-UDP transferase and low levels were detected. This observation also points to an alteration in the rate of biosynthesis of chloramphenicol.